COAGULANTS & ANTICOAGULANTS

LEARNING OBJECTIVES

BY the end of Lecture, student should be able to

• Define what are anticoagulants.

• Define what are coagulants.

• Classify the medicines in this group.

• Enumerate their salient features.

• Describe their mechanism of action.

• Enumerate when they should be used.

• Enlist when they should not be used.

• Enlist their bad effects.

COAGULANTS & ANTICOAGULANTS

LECTURE OUTLINE

WHAT IS BLOOD?

• Connective tissue.

• Balance between thrombosis & haemorrhage.

• Blood maintains haemostasis.

COAGULANTS:

Definition: An agent that produces coagulation (Coagulation is a complex process by which blood forms clots).

ANTICOAGULANTS

Definition: An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting.

COAGULATION FACTORS:

• I Fibrinogen.

• II Prothrombin.

• III Tissue factor.

• IV Calcium.

• V Proaccelerin, labile factor.

• VI Accelerin.

• VII Stable factor.

• VIII Antihemophilic factor.

• IX Christmas factor.

• X Stuart-Prowers factor.

• XI Plasma thromboplastin antecedent.

• XII Hageman factor.

• XIII Fibrin-stabilizing factor.

NATURAL ANTICOAGULANTS:

1. PGI-2.

2. Antithrombin.

3. Protein-C.

4. TFPI.

5. Heparin.

6. Fibrinolytic system.

CLASSIFICATION:

A) Anticoagulants.

B) Thrombolytic agents.

C) Antiplatelet agents.

ANTICOAGULANTS:

1. Parenteral

• Heparin Sulphate.

• Danaparoid.

• Lepirudin.

2. Oral

• Warfarin sodium.

• Dicumarol.

• Phenprocoumon.

• Acenocoumarol.

• Anisindione.

THROMBOLYTIC AGENTS:

• Streptokinase.

• t-PA.

• Urokinase.

• Alteplase.

ANTIPLATELET AGENTS:

• Aspirin

• Dipyridamole

• Ticlopidine

• Clopidogrel

HEPARIN SULPHATE:

• Glycosaminoglycan found in mast cells.

• UDP sugar precursors.

• Extracted from porcine intestinal mucosa or bovine lung.

• Available as USP units/mg.

• LMWH are 4500 daltons or 15 monosaccharide units.

• Isolated from standard heparin.

Mechanism of action:

• Acts via heparin co-factor or antithrombin III.

• Inhibits thrombin by PAI-1, protein-C inhibitor & protease nexin-1.

• Inhibits factor Xa by TFPI.

• Releases lipoprotein lipase enzyme.

• Interferes with platelet aggregation.

WHEN TO BE USED (Indications):

WHEN THROMBI ARE FORMED IN

• Brain.

• Abdomen.

• Heart.

• Venous or arterial catheters.

• Performing procedures

 Coronary angiography.

 Haemodialysis.

What are their bad effects? (Adverse effects)

• Bleeding.

• Allergy.

• Increase in serum potassium level (Hyperkalaemia).

• Decrease in platelet count (Thrombocytopenia).

• Softening of bones (Osteoporosis).

• Loss of hairs (Alopecia).

When they should not be used (Contraindications):

• Hemorrhagic disorders

• Thrombocytopenia (platelets < 80 x 109/L)

• Bleeding from esophagus, stomach, brain etc.

• Bleeding from any major trauma

• Hypersensitivity to heparin

ORAL ANTICOAGULANTS:

Warfarin sodium:

• Synthetic derivative of coumarin.

• Found naturally in plants e.g. woodruff.

• Act by inhibiting vitamin-K epoxide reductase.

• It recycles oxidated vitamin-K to its reduced form.

• Also known as vitamin-K antagonists.

Mechanism of action:

• Act by inhibiting the synthesis of vitamin-k dependent clotting factors that is II, VII, IX & X

• Inhibit synthesis of regulatory factors like protein C, S & Z

• Warfarin inhibits epoxide reductase & diminishes available Vit-K & its reduced form in the tissues.

BAD EFFECTS (Adverse effects):

• Haemorrhage

• Abortion

• Warfarin syndrome

• Itching of skin

• Purple toe.

USES (Indications):

• Thrombosis

• Embolism in pulmonary & coronary circulation.

Heparin:

• Heparin is a large polymer

• Given parenterally

• Acts in blood

• Rapid onset of action

• Activates anti-thrombin III

• Monitored by APTT

• Protamine sulphate

• Mostly used for acute purposes

• Used in pregnancy

Warfarin:

• Warfarin is a small lipid soluble molecule

• Given per orally

• Acts in liver

• Slow onset of action

• Impairs synthesis of factor II, VII, IX & X

• Monitored by PT/ INR

• Vitamin-K & plasma

• Mostly used for chronic purposes

• Not used in pregnancy.

THROMBOLYTICS
Sources:

• Thrombolytic drugs are derived from Streptomyces spp.

• Recombinant technology.

• Manufactured by bacteria like streptokinase etc.

Mechanism:

• Work by activating the enzyme plasminogen

• Clears the cross-linked fibrin mesh

• Makes the clot soluble

• Followed by proteolysis

• Blood flow in the occluded blood vessels is therefore restored.

BAD EFFECTS
(Adverse effects):

Bleeding because of

• Local fibrinolysis.

• Systemic fibrinogenolysis.

• Destruction of coagulation factors V & VIII.

Antiplatelet agents:

• Decrease platelet aggregation.

• Inhibit thrombus formation.

• Effective in the arterial circulation.

• Used in primary and secondary prevention of thrombosis.

• E.g aspirin.

Coagulants:

• VITAMIN- K

• PLASMA FRACTIONS

• CRYOPRECIPITATE

• DESMOPRESSIN ACETATE

• FIBRINOLYTIC INHIBITORS

1. Aminocaproic acid.

2. Tranexemic acid.

• SERINE PROTEASE INHIBITORS

1. Aprotinin.

VITAMIN -K

• Group of lipophilic, hydrophobic vitamins.

• Needed for the post-translational modification of coagulation proteins.

• Phylloquinone (vitamin K1) is the major dietary form of vitamin K.

• Vitamin K2 (menaquinone, menatetrenone) is produced by bacteria in the intestines.

2. PLASMA FRACTIONS:

a) Fresh frozen plasma.

b) Platelets.

c) Plasma concentrates.

d) Non-plasma recombinant factor concentrates.